Cancers (malignant tumors) now occupy approximately 30 percent of the cause of death in Japan. In particular, pancreas cancer is one of intractable cancers, the 5 year-survival rate of the all patients is estimated to be 2 to 3%. The number of patients died of pancreas cancer has rapidly been increased approximately 2.5 times during a period of the last 20 years, and according to the statics in 2009, 26,791 patients died of pancreas cancer. The number of onset is approximately the same as the number of death, which occupies 6% of the cause of death due to cancers in Japan, and the number of death in pancreas cancer is ranked in fifth position following the cancers in other regions, lung, stomach, large intestine, and liver.
Therapy by which a radical cure is expected depends only on surgical excision, but as the pancreas cancer is found in a state of progressive cancer (stage III+IV) in most of the patients, it is practically said that the cases in which radical excision can be applied are at most 10-20% of the total patients of pancreas cancer. For every stages, the median of the survival period is about 12-30 months in the stages I and II, 9-11 months in the stage III, and 5-6 months in the stage IV, indicating that the prognosis is extremely poor and it is considered that there is almost no possibility to cure particularly inpatients with the pancreas cancer which cannot be excised.
The standard therapy for a progressive pancreas cancer is based on gemcitabine, and when gemcitabine results in a refractory state, there is no standardized therapy established. In some progressive pancreas cancer patients, a general condition seems well even after they become refractory to gemcitabine. It has been considered accordingly that development of an effective therapeutic method in such a group of patients (pancreas cancer refractory to gemcitabine) is an important problem all over the development of a therapeutic method for pancreas cancer.
In recent years, it has been reported that the cells derived from pancreas cancer such as PANC-1, AsPC-1, BxPC-1 and KP-3 show a strong resistance even in an extreme nutritional deficiency state, and the removal of this resistance would possibly lead to a new biochemical approach in the cancer therapy (Patent Document 1: which is hereby incorporated by reference in its entirety).
It has been reported that arctigenin is effective in a screening of substances which can remove the viability of tumor cells in a low nutritional state using a pancreas cancer cell strain PANC-1 (Non-Patent Document 1: which is hereby incorporated by reference in its entirety).
In addition, the cancer stem cells have self-replication competence and pluripotency, and thus exhibit a strong tumor-producing ability to form cancers from a small number of cells at a high rate.
It has been pointed out that in tumor tissues a large number of immature blood vessels are formed with sudden increase of the tissues, resulting in circulatory failure in the tissues to cause not only hypoxia and undernutrition but also the influence on the delivery of anticancer agents. On the other hand, the cancer stem cells show resistance to a number of anticancer agents and radiation and cause metastasis, which greatly disturb the cancer therapy. It is known that the stem cells are highly induced in such a specific micro-environment as especially hypoxia and undernutrition among the cancer tissue.
Accordingly, it is considered that the development of a therapeutic method for targeting the cancer stem cells or a method for normalizing the blood vessel by inhibition of angiogenesis might greatly contribute to the anticancer therapy.